Functional Genomics and Genetics Shared Resource - Project Summary/Abstract The Functional Genomics and Genetics Shared Resource provides members of the CSHL Cancer Center with access to advanced RNAi and CRISPR screening technologies and services deriving genetically engineered cells and animals. This Shared Resource was recently established through reorganization and integration of services from the Microarray and RNA Quantitation Shared Resource, the Gene Targeting Shared Resource, and new technologies for shRNA and CRISPR screening. The recent revolution in sequencing technology has facilitated the collection of massive amounts of human genomic and expression data. To understand the human cancer genome and reveal therapeutic opportunities, a complementary set of functional genomics tools is required to systematically discover pathway relationships among genes. It is the goal of the Functional Genomics and Genetics Shared Resource to leverage its innovative approaches to RNAi and genome editing to promote discovery of new therapeutic targets and to create disease relevant models for improving human health. A major focus of this Shared Resource is in assisting investigators with the design, implementation, and data analysis of multi-plexed RNAi/CRISPR screens in mammalian cells. Functional genomic screening is primarily provided as a Shared Resource-assisted service with some full-service screening options. In addition, the Shared Resource also offers full-service construction of custom RNAi/CRISPR plasmid libraries. In order to extend functional assessment of genetic contributions in the context of genetically engineered cells and mice, this Shared Resource provides production of genetically modified mice using Cas9 and single guide RNA (sgRNA) microinjection into 1-cell mouse zygotes. A range of other gene targeting services, including gene targeting in mouse embryonic stem (ES) cells, derivation of ES cells from mouse models, production of chimeric mice by blastocyst injection, production of transgenic mice by pronuclear injection, cryopreservation/recovery of embryo and sperm, and in vitro fertilization are also available. Re-derivation of animals through this Shared Resource is also a key service for maintaining a pathogen-free animal facility. This Shared Resource will be vital to the Cancer Center because it will enable scientists to use genetic screening tools to discover novel cancer genes, therapeutic targets, and mechanisms of drug resistance and for developing new animal models of cancer for pre-clinical studies. Over the last grant period, 18 Cancer Center members (49% of the membership) used the combined services of the new Shared Resource.